tbuckley/cabot-search huggingface dataset:
First-phase insulin secretion: can its evaluation direct therapeutic approaches?
Authors: Gianfranco Di Giuseppe, Gea Ciccarelli, Laura Soldovieri, Umberto Capece, Chiara M.A. Cefalo, Simona Moffa, Enrico C. Nista, Michela Brunetti, Francesca Cinti, Antonio Gasbarrini, Alfredo Pontecorvi, Andrea Giaccari, Teresa Mezza
Journal: Trends in Endocrinology and Metabolism (2023)

Our work is aimed at unraveling the role of the first-phase insulin secretion in the natural history of type 2 diabetes mellitus (T2DM) and its interrelationship with insulin resistance and with β cell function and mass. Starting from pathophysiology, we investigate the impact of impaired secretion on glucose homeostasis and explore postmeal hyperglycemia as the main clinical feature, underlining its relevance in the management of the disease. We also review dietary and pharmacological approaches aimed at improving early secretory defects and restoring residual β cell function. Furthermore, we discuss possible approaches to detect early secretory defects in clinical practice. By providing a journey through human and animal data, we attempt a unification of the recent evidence in an effort to offer a new outlook on β cell secretion.
Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial
Authors: Kevin Talboom, Wernard A A Borstlap, Sapho X Roodbeen, Emma R J Bruns, Christianne J Buskens, Roel Hompes, Kristien M A J Tytgat, Jurriaan B Tuynman, Esther C J Consten, Gijsbert Heuff, Teaco Kuiper, Anna A W van Geloven, Gerrit J Veldhuis, Joost A B van der Hoeven, Steve M M De Castro, Colin Sietses, Antonino Spinelli, Anthony W H van de Ven, Edwin S van der Zaag, Marinke Westerterp, Henderik L van Westreenen, Marcel L Dijkgraaf, Nicole P Juffermans, Wilhelmus A Bemelman, Annette A van Zweeden, Daniel Hess, Hilko A Swank, Lisette Scholten, Jarmila D W van der Bilt, Marilou A Jansen, Peter van Duijvendijk, Donna Bezuur, Michele Carvello, Caterina Foppa, Wouter H de Vos tot Nederveen Cappel, Ritch T J Geitenbeek, Lara van Woensel, Steve M M De Castro, Caroline Wientjes, Stefan van Oostendorp
Journal: The Lancet Haematology (2023)
Annals Graphic Medicine - Patient Other
Authors: Melanie Ortiz Alvarez de la Campa
Journal: Annals of Internal Medicine (2023)

Web ExclusivesMarch 2023Annals Graphic Medicine - Patient OtherFREEMelanie Ortiz Alvarez de la Campa, BSMelanie Ortiz Alvarez de la Campa, BSPathobiology Graduate Program, Brown University, Providence, Rhode Island (M.O.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0033 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Melanie Ortiz Alvarez de la Campa, BSAffiliations: Pathobiology Graduate Program, Brown University, Providence, Rhode Island (M.O.D.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0033.Author/Illustrator Information: Melanie Ortiz Alvarez de la Campa, BS, is a Pathobiology PhD Student and Digital Artist at Brown University. For more of their work, please visit https://lnk.bio/7Vdw (e-mail, melanie_ortiz@brown.edu).This article was published at Annals.org on 28 February 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics March 2023Volume 176, Issue 3 ePublished: 28 February 2023 Issue Published: March 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study
Authors: Gianni Bisogno, Veronique Minard-Colin, Ilaria Zanetti, Andrea Ferrari, Soledad Gallego, Raquel Dávila Fajardo, Henry Mandeville, Anna Kelsey, Rita Alaggio, Daniel Orbach, Sheila Terwisscha van Scheltinga, Gabriela Guillén Burrieza, Myriam Ben-Arush, Heidi Glosli, Peter Mudry, Sima Ferman, Christine Devalck, Anne Sophie Defachelles, Johannes Hendrikus Maria Merks, Meriel Jenney
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The RMS2005 study included two phase III randomized trials for high-risk (HR) and observational trials for low (LR), standard (SR), and very high-risk (VHR) patients who have been partially reported. Herein, we present a comprehensive report of results achieved for the complete unselected nonmetastatic cohort and analyze the evolution of treatment in comparison with previous European protocols. After a median follow-up of 73.1 months, the 5-year event-free survival (EFS) and overall survival (OS) of the 1,733 patients enrolled were 70.7% (95% CI, 68.5 to 72.8) and 80.4% (95% CI, 78.4 to 82.3), respectively. The results by subgroup: LR (80 patients) EFS 93.7% (95% CI, 85.5 to 97.3), OS 96.7% (95% CI, 87.2 to 99.2); SR (652 patients) EFS 77.4% (95% CI, 73.9 to 80.5), OS 90.6% (95% CI, 87.9 to 92.7); HR (851 patients) EFS 67.3% (95% CI, 64.0 to 70.4), OS 76.7% (95% CI, 73.6 to 79.4); and VHR (150 patients) EFS 48.8% (95% CI, 40.4 to 56.7), OS 49.7% (95% CI, 40.8 to 57.9). The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries with the confirmation of a 22-week vincristine/actinomycin D regimen for LR patients, the reduction of the cumulative ifosfamide dose in the SR group, and for HR disease, the omission of doxorubicin and the addition of maintenance chemotherapy.
Evolving Landscape of Metastatic Cancer Survivorship: Reconsidering Clinical Care, Policy, and Research Priorities for the Modern Era
Authors: Julia Lai-Kwon, Sarah Heynemann, Nicolas H. Hart, Raymond J. Chan, Thomas J. Smith, Larissa Nekhlyudov, Michael Jefford
Journal: Journal of Clinical Oncology (2023)

Reconceptualizing Survivorship for the Modern Cancer EraAn individual may be considered a cancer survivor from diagnosis through the balance of their life. 1In contrast to those with early-stage cancer, survivorship care for people with metastatic cancer has only recently begun to receive significant attention, 2-6 partly due to recent therapeutic advances and improvements in survival.There have been growing calls from patient advocates to address the unmet supportive care needs of people with metastatic cancer 4,7 and assurance that they and their caregivers be included within the definition of cancer survivor outlined by the National Coalition for Cancer Survivorship.
Long-Term Changes in the Size of Pituitary Microadenomas
Authors: Dawid Hordejuk, Yee-Ming M. Cheung, Wei Wang, Timothy Smith, Edward Laws, Ursula B. Kaiser, Le Min
Journal: Annals of Internal Medicine (2023)

The estimated prevalence of pituitary lesions is 10% to 38.5% in radiologic studies. However, how frequently these incidental lesions should be monitored by serial pituitary magnetic resonance imaging (MRI) remains unclear.To evaluate changes in pituitary microadenomas over time.Retrospective, longitudinal cohort study.Mass General Brigham, Boston, Massachusetts.Evidence of pituitary microadenoma from MRI.Dimensions of pituitary microadenomas.During the study period (from 2003 to 2021), 414 patients with pituitary microadenomas were identified. Of the 177 patients who had more than 1 MRI, 78 had no change in the size of the microadenoma over time, 49 had an increase in size, 34 had a decrease in size, and 16 had both an increase and decrease in size. By linear mixed model analysis, the estimated slope was 0.016 mm/y (95% CI, -0.037 to 0.069). In the subgroup analysis, pituitary adenomas with a baseline size of 4 mm or less tended to increase in size. The estimated slope was 0.09 mm/y (CI, 0.020 to 0.161). In contrast, in the subgroup with baseline tumor size greater than 4 mm, the size tended to decrease. The estimated slope was -0.063 mm/y (CI, -0.141 to 0.015).Retrospective cohort, some patients were lost to follow-up for unknown reasons, and data were limited to local large institutions.During the study period, approximately two thirds of the microadenomas remained unchanged or decreased in size. The growth, if any, was slow. These findings suggest that less frequent pituitary MRI surveillance for patients with incidental pituitary microadenomas may be safe.None.
When Less Can Be More: How the 10-Year Updated Results From the Randomized Controlled AMAROS Trial Should Affect Axillary Management in the Setting of a Positive Node
Authors: Laura J. Esserman, Hirra Ali, Tesia McKenzie
Journal: Journal of Clinical Oncology (2023)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.It is important to reflect on how far we as a medical community have come when treating breast cancer. Ongoing research, clinical trials, and better understanding of biology have transformed our understanding and treatment of breast cancer. There is still much to learn. Although progress was slow for decades, treatments have evolved more quickly in the recent past. The Halsted radical mastectomy, first popularized in 1894, was performed for almost a century, and although it decreased local recurrence, it did not improve survival. This well-intentioned surgery disfigured women and was abandoned as better systemic therapies were introduced and less aggressive surgical procedures were found to be equivalent in clinical trials. The evolution of trials in the modern era has taught us an important lesson. De-escalation of surgical interventions in the setting of improved systemic therapy can lead to better patient outcomes. We present a case of a clinician with an early-stage invasive ductal carcinoma responsive to neoadjuvant endocrine therapy and who subsequently underwent a partial mastectomy with axillary sentinal lymph node biopsy. Although clinically node-negative, she was pathologically node-positive, and concerned about both optimizing her outcomes and minimizing the risk of lymphedema. The release of 10-year follow-up data from the AMAROS trial furthers our knowledge and understanding of the impact of local control measures of the axilla. The concepts illustrated by the findings of AMAROS may be applied in clinical practice and ultimately help us make rational treatment choices and support shared decision making for patients like ours.
Influence of Pore Size in Protein G'‐Grafted Mesoporous Silica Nanoparticles as a Serum Pretreatment System for In Vitro Allergy Diagnosis
Authors: Juan L. Paris, Cristina Monío, Ana M. Pérez‐Moreno, Raquel Jurado‐Escobar, Gador Bogas, Tahía D. Fernández, María I. Montañez, Cristobalina Mayorga, María J. Torres
Journal: Advanced Healthcare Materials (2023)

Particles with the capacity to bind to immunoglobulin G (IgG) can be used for the purification of IgG or to process clinical samples for diagnostic purposes. For in vitro allergy diagnosis, the high IgG levels in serum can interfere with the detection of allergen-specific IgE, the main diagnostic biomarker. Although commercially available, current materials present a low IgG capture capacity at large IgG concentrations or require complex protocols, preventing their use in the clinic. In this work, mesoporous silica nanoparticles are prepared with different pore sizes, to which IgG-binding protein G' is grafted. It is found that for one particular optimal pore size, the IgG capture capacity of the material is greatly enhanced. The capacity of this material to efficiently capture human IgG in a selective way (compared to IgE) is demonstrated in both solutions of known IgG concentrations as well as in complex samples, like serum, from healthy controls and allergic patients using a simple and fast incubation protocol. Interestingly, IgG removal using the best-performing material enhances in vitro IgE detection in sera from patients allergic to amoxicillin. These results highlight the great translation potential of this strategy to the clinic in the context of in vitro allergy diagnosis.
Comparison of new psychiatric diagnoses among Finnish children and adolescents before and during the COVID-19 pandemic: A nationwide register-based study
Authors: David Gyllenberg, Kalpana Bastola, Wan Mohd Azam Wan Mohd Yunus, Kaisa Mishina, Emmi Liukko, Antti Kääriälä, Andre Sourander
Journal: PLoS Medicine (2023)

Coronavirus Disease 2019 (COVID-19) restrictions decreased the use of specialist psychiatric services for children and adolescents in spring 2020. However, little is known about the pattern once restrictions eased. We compared new psychiatric diagnoses by specialist services during pandemic and pre-pandemic periods.This national register study focused on all Finnish residents aged 0 to 17 years from January 2017 to September 2021 (approximately 1 million a year). The outcomes were new monthly diagnoses for psychiatric or neurodevelopmental disorders in specialist services. These were analyzed by sex, age, home location, and diagnostic groups. The numbers of new diagnoses from March 2020 were compared to predictive models based on previous years. The predicted and observed levels in March to May 2020 showed no significant differences, but the overall difference was 18.5% (95% confidence interval 12.0 to 25.9) higher than predicted in June 2020 to September 2021, with 3,821 more patients diagnosed than anticipated. During this period, the largest increases were among females (33.4%, 23.4 to 45.2), adolescents (34.4%, 25.0 to 45.3), and those living in areas with the highest COVID-19 morbidity (29.9%, 21.2 to 39.8). The largest increases by diagnostic groups were found for eating disorders (27.4%, 8.0 to 55.3), depression and anxiety (21.0%, 12.1 to 51.9), and neurodevelopmental disorders (9.6%, 3.0 to 17.0), but psychotic and bipolar disorders and conduct and oppositional disorders showed no significant differences and self-harm (-28.6, -41.5 to -8.2) and substance use disorders (-15.5, -26.4 to -0.7) decreased in this period. The main limitation is that data from specialist services do not allow to draw conclusions about those not seeking help.Following the first pandemic phase, new psychiatric diagnoses in children and adolescents increased by nearly a fifth in Finnish specialist services. Possible explanations to our findings include changes in help-seeking, referrals and psychiatric problems, and delayed service access.
Referral to the NHS Diabetes Prevention Programme and conversion from nondiabetic hyperglycaemia to type 2 diabetes mellitus in England: A matched cohort analysis
Authors: Rathi Ravindrarajah, Matt Sutton, David Reeves, Sarah Cotterill, Emma Mcmanus, Rachel Meacock, William Whittaker, Claudia Soiland-Reyes, Simon Heller, Peter Bower, Evangelos Kontopantelis
Journal: PLoS Medicine (2023)

Background The NHS Diabetes Prevention Programme (NDPP) is a behaviour change programme for adults who are at risk of developing type 2 diabetes mellitus (T2DM): people with raised blood glucose levels, but not in the diabetic range, diagnosed with nondiabetic hyperglycaemia (NDH). We examined the association between referral to the programme and reducing conversion of NDH to T2DM. Methods and findings Cohort study of patients attending primary care in England using clinical Practice Research Datalink data from 1 April 2016 (NDPP introduction) to 31 March 2020 was used. To minimise confounding, we matched patients referred to the programme in referring practices to patients in nonreferring practices. Patients were matched based on age (≥3 years), sex, and ≥365 days of NDH diagnosis. Random-effects parametric survival models evaluated the intervention, controlling for numerous covariates. Our primary analysis was selected a priori: complete case analysis, 1-to-1 practice matching, up to 5 controls sampled with replacement. Various sensitivity analyses were conducted, including multiple imputation approaches. Analysis was adjusted for age (at index date), sex, time from NDH diagnosis to index date, BMI, HbA1c, total serum cholesterol, systolic blood pressure, diastolic blood pressure, prescription of metformin, smoking status, socioeconomic status, a diagnosis of depression, and comorbidities. A total of 18,470 patients referred to NDPP were matched to 51,331 patients not referred to NDPP in the main analysis. Mean follow-up from referral was 482.0 (SD = 317.3) and 472.4 (SD = 309.1) days, for referred to NDPP and not referred to NDPP, respectively. Baseline characteristics in the 2 groups were similar, except referred to NDPP were more likely to have higher BMI and be ever-smokers. The adjusted HR for referred to NDPP, compared to not referred to NDPP, was 0.80 (95% CI: 0.73 to 0.87) ( p &lt; 0.001). The probability of not converting to T2DM at 36 months since referral was 87.3% (95% CI: 86.5% to 88.2%) for referred to NDPP and 84.6% (95% CI: 83.9% to 85.4%) for not referred to NDPP. Associations were broadly consistent in the sensitivity analyses, but often smaller in magnitude. As this is an observational study, we cannot conclusively address causality. Other limitations include the inclusion of controls from the other 3 UK countries, data not allowing the evaluation of the association between attendance (rather than referral) and conversion. Conclusions The NDPP was associated with reduced conversion rates from NDH to T2DM. Although we observed smaller associations with risk reduction, compared to what has been observed in RCTs, this is unsurprising since we examined the impact of referral, rather than attendance or completion of the intervention.
Treatment with Mesenchymal Stem Cell‐Derived Nanovesicle‐Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization
Authors: Liying Pang, Hong Jin, Zhengmao Lu, Fangyuan Xie, Huaxing Shen, Xinying Li, Xinyi Zhang, Xianghe Jiang, Lili Wu, Mengya Zhang, Tinglin Zhang, Yonghua Zhai, Yuanyuan Zhang, Huilin Guan, Jiacan Su, Meng Li, Jie Gao
Journal: Advanced Healthcare Materials (2023)

Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell (MSC)-derived exosomes is a promising therapeutic strategy in osteoarthritis treatment. However, the poor yield of exosomes is an obstacle to the use of this modality in the clinic. Herein, a promising strategy is developed to fabricate high-yield exosome-mimicking MSC-derived nanovesicles (MSC-NVs) with enhanced regenerative and anti-inflammatory capabilities. MSC-NVs are prepared using an extrusion approach and are found to increase chondrocyte and human bone marrow MSC differentiation, proliferation, and migration, in addition to inducing M2 macrophage polarization. Furthermore, gelatin methacryloyl (GelMA) hydrogels loaded with MSC-NVs (GelMA-NVs) are formulated, which exhibit sustained release of MSC-NVs and are shown to be biocompatible with excellent mechanical properties. In a mouse osteoarthritis model constructed by surgical destabilization of the medial meniscus (DMM), GelMA-NVs effectively ameliorate osteoarthritis severity, reduce the secretion of catabolic factors, and enhance matrix synthesis. Furthermore, GelMA-NVs induce M2 macrophage polarization and inflammatory response inhibition in vivo. The findings demonstrate that GelMA-NVs hold promise for osteoarthritis treatment through modulation of chondrogenesis and macrophage polarization.
Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure
Authors: Emerson C. Perin, Kenneth M. Borow, Timothy D. Henry, Farrell O. Mendelsohn, Leslie W. Miller, Elizabeth Swiggum, Eric D. Adler, David H. Chang, R. David Fish, Alain Bouchard, Margaret Jenkins, Alex Yaroshinsky, Jack Hayes, Olga Rutman, Christopher W. James, Eric Rose, Silviu Itescu, Barry Greenberg
Journal: Journal of the American College of Cardiology (2023)

Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF. This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity. The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L). The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.
Association Between Shock Etiology and 5-Year Outcomes After Venoarterial Extracorporeal Membrane Oxygenation
Authors: Pichoy Danial, Maud-Emmanuel Olivier, Nicolas Bréchot, Maharajah Ponnaiah, Thibaut Schoell, Cosimo D'Alessandro, Pierre Demondion, Marina Clément, Charles Juvin, Aude Carillion, Adrien Bouglé, Alain Combes, Pascal Leprince, Guillaume Lebreton
Journal: Journal of the American College of Cardiology (2023)
Initial Findings From the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures
Authors: Jonathan C. Hsu, Douglas Darden, Chengan Du, Joseph E. Marine, Sheila Nichols, Gregory M. Marcus, Andrea Natale, Peter A. Noseworthy, Kimberly A. Selzman, Paul Varosy, Frederick Masoudi, James Freeman, Jeptha Curtis, Joseph Akar, Peter R. Kowey
Journal: Journal of the American College of Cardiology (2023)